| Summary: | 碩士 === 長庚大學 === 天然藥物研究所 === 97 === Apomorphine is a non-selective agonist of D1 and D2 dopamine receptors. Apomorphine is a very effective drug in the management of ‘on-off’ motor response fluctuations in the treatment of Parkinson’s disease. The aim of this present work was to develop acoustically active lipid-coated microbubbles for encapsulation of both apomorphine hydrochloride and apomorphine base to circumvent these delivery problems. The lipid-coated microbubbles were prepared using coconut oil and perfluoropentane as the inner phase, which was emulsified by phospholipids and cholesterol. The lipid-coated microbubbles were characterized in terms of their morphology, size, zeta potential, and drug release. The lipid-coated microbubbles particle size ranged about from 150 to 380 nm, with the differences in changing the coconut oil or perfluoropentane ratio in the formulations. The atomic force microscopy confirmed an oval- or raisin-shaped particle and narrow size-distribution of these systems. Ultrasound imaging confirmed the echogenic activity of lipid-coated microbubbles developed in this study. The stability experiment results indicated that lipid-coated microbubbles could protect apomorphine from degradation in the circulation. The evaporation of lipid-coated microbubbles at 37 °C was also limited. apomorphine hydrochloride and apomorphine base in lipid-coated microbubbles showed retarded and sustained release. Using a 1 MHz ultrasound, an increased release of apomorphine hydrochloride in the presence of plasma could be established, illustrating a possible drug-targeting effect. On the contrary, apomorphine base showed a decreased release by ultrasound application. The lipid-coated microbubbles loading with apomorphine showed promised stability and safety. They were successful in sustaining apomorphine delivery.
Selegiline, also commonly referred to in the clinical and pharmacological literature as L-deprenyl, is an acetylenic derivative of phenethylamine. It acts as an irreversible inhibitor of monoamine oxidase type B (MAO-B), an intracellular enzyme associated with the outer membrane of mitochondria. The present work was aimed to design a transdermal systems of selegiline using hydrogel-based drug reservoir and rate controlling membrane (Solupor polyethylene membrane). Both Solupor membrane and hydrogel showed a cross-linking structure with micropores. Various skin membrance, including nude mice skin, porcine skin, stratum corneum (SC)-stripped skin, delipidized skin and cellulose membrane, were used as permeation barrier to elucidate the mechanisms and pathyway. Drug transfer through Solupor but not hydrogel has been demonstrated to be the rate-limiting step when incorporating the membrane and hydrogel together as the delivery system. The inter-subject variation from the skin was greatly reduced by both Solupor membrane and hydrogel. The results of this study encourage the further investigation of hydrogel-membrane delivery systems for transdermal selegiline administration.
|
|---|
